DESCRIPTION (Adapted from applicant's description): The goals of this project are to test the hypothesis that skeletal pattern formation in the vertebrate limb arises, in part, from the intrinsic, self-organizing properties of limb bud precartilage mesenchymal tissue. The focus of the studies will be on the regulatory mechanisms of fibronectin's spatiotemporal expression in limb mesenchyme in vitro and in vivo. Specific aims are: 1) to identify the sequences of the fibronectin promoter that are involved in the spatiotemporal expression of fibronectin during limb mesenchymal condensation and to delineate candidate sites for the binding of developmentally relevant transcription factors; and 2) to test the hypothesis that endogenous factors of the developing limb such as TGF-beta, FGF-2 and -4, and retinoic acid, regulate chondrogenic pattern formation via fibronectin gene expression.